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K Davidson

Publications and source records attributed to K Davidson.

At least 19 recordsLinked to original sources
PubMed2006

Signalling through Class I PI3Ks in mammalian cells.

It is now accepted that activation of Class I PI3Ks (phosphoinositide 3-kinases) is one of the most important signal transduction pathways used by cell-surface receptors to control intracellular events. The receptors which access this pathway include those that recognize growth factors, hormones, antigens and inflammatory stimuli, and the cellular events known to be regulated include cell growth, survival, proliferation and movement. We have learnt a great deal about the family of Class I PI3K enzymes themselves and the structural adaptations which allow a variety of cell-surface receptors to regulate their activity. Class I PI3Ks synthesize the phospholipid PtdIns(3,4,5)P3 in the membranes in which they are activated, and it is now accepted that PtdIns(3,4,5)P3 and its dephosphorylation product PtdIns(3,4)P2 are messenger molecules which regulate the localization and function of multiple effectors by binding to their specific PH (pleckstrin homology) domains. The number of direct PtdIns(3,4,5)P3/PtdIns(3,4)P2 effectors which exist, even within a single cell, creates an extremely complex signalling web downstream of PI3K activation. Some key players are beginning to emerge, however, linking PI3K activity to specific cellular responses. These include small GTPases for the Rho and Arf families which regulate the cytoskeletal and membrane rearrangements required for cell movement, and PKB (protein kinase B), which has important regulatory inputs into the regulation of cell-cycle progression and survival. The importance of the PI3K signalling pathway in regulating the balance of decisions in cell growth, proliferation and survival is clear from the prevalence of oncogenes (e.g. PI3Kalpha) and tumour suppressors [e.g. the PtdIns(3,4,5)P3 3-phosphatase, PTEN (phosphatase and tensin homologue deleted on chromosome 10)] found in this pathway. The recent availability of transgenic mouse models with engineered defects in Class I PI3K signalling pathways, and the development of PI3K isoform-selective inhibitors by both academic and pharmaceutical research has highlighted the importance of specific isoforms of PI3K in whole-animal physiology and pathology, e.g. PI3Kalpha in growth and metabolic regulation, PI3Kbeta in thrombosis, and PI3Kdelta and PI3Kgamma in inflammation and asthma. Thus the Class I PI3K signalling pathway is emerging as an exciting new area for the development of novel therapeutics.

Animals↗
PubMed2004

Therapist competence and clinical outcome in the Prevention of Parasuicide by Manual Assisted Cognitive Behaviour Therapy trial: the POPMACT study.

BACKGROUND: Therapist competence may be an important factor in determining clinical outcome in psychological therapies. However, there are few published studies of therapist competence v. patient outcome from randomized controlled trials. We tested the hypothesis that higher levels of therapist competence would lead to better clinical outcomes in both patient- and observer-rated measures at 6- and 12-month follow-up. METHOD: A random sample of 49 audiotapes of manual assisted cognitive therapy sessions delivered by 21 therapists involved in the Prevention of Parasuicide by Manual Assisted Cognitive Behaviour Therapy trial was rated to assess the level of therapist competence. Patient outcome was assessed using self and observer ratings of depressive and anxiety symptoms, social functioning, global functioning and number of episodes of deliberate self-harm. RESULTS: At 6-month follow-up, there was a statistically significant association between therapist level of competence and observer-rated depression only. At 12-month follow-up, significant associations were noted between therapist competence and all observer-rated clinical outcomes but not for self-rated outcome measures. However, there was no association between therapist competence and the number of self-harm episodes during follow-up. CONCLUSIONS: When treated by therapists rated as more competent than other therapists who received equivalent brief training, patients with recurrent self-harm show significant clinical improvements. However, this benefit is not identified across all outcome measures and is not fully apparent until 12-month follow-up.

Adult↗
PubMed2003

Randomized controlled trial of brief cognitive behaviour therapy versus treatment as usual in recurrent deliberate self-harm: the POPMACT study.

BACKGROUND: We carried out a large randomized trial of a brief form of cognitive therapy, manual-assisted cognitive behaviour therapy (MACT) versus treatment as usual (TAU) for deliberate self-harm. METHOD: Patients presenting with recurrent deliberate self-harm in five centres were randomized to either MACT or (TAU) and followed up over 1 year. MACT patients received a booklet based on cognitive behaviour therapy (CBT) principles and were offered up to five plus two booster sessions of CBT from a therapist in the first 3 months of the study. Ratings of parasuicide risk, anxiety, depression, social functioning and global function, positive and negative thinking, and quality of life were measured at baseline and after 6 and 12 months. RESULTS: Four hundred and eighty patients were randomized. Sixty per cent of the MACT group had both the booklet and CBT sessions. There were seven suicides, five in the TAU group. The main outcome measure, the proportion of those repeating deliberate self-harm in the 12 months of the study, showed no significant difference between those treated with MACT (39%) and treatment as usual (46%) (OR 0.78, 95% CI 0.53 to 1.14, P=0.20). CONCLUSION: Brief cognitive behaviour therapy is of limited efficacy in reducing self-harm repetition, but the findings taken in conjunctin with the economic evaluation (Byford et al. 2003) indicate superiority of MACT over TAU in terms of cost and effectiveness combined.

Adult↗
PubMed2003

Cost-effectiveness of brief cognitive behaviour therapy versus treatment as usual in recurrent deliberate self-harm: a decision-making approach.

BACKGROUND: Deliberate self-harm can be costly, in terms of treatment and subsequent suicide. Any intervention that reduces episodes of self-harm might therefore have a major impact on the costs incurred by service providers and the productivity losses due to illness or premature death. METHOD: Four hundred and eighty patients with a history of recurrent deliberate self-harm were randomized to manual-assisted cognitive behaviour therapy (MACT) or treatment as usual. Economic data were collected from patients at baseline, 6 and 12 months, and these data were complete for 397 patients. Incremental cost-effectiveness was explored using the primary outcome measure, proportion of patients having a repeat episode of deliberate self-harm, and quality of life. The uncertainty surrounding costs and effects was represented using cost-effectiveness acceptability curves. RESULTS: Differences in total cost per patient were statistically significant at 6 months in favour of MACT (pounds sterling -897, 95 % CI -1747 to -48, P=0.04), but these differences did not remain significant at 12 months (pounds sterling -838, 95% CI -2142 to 466, P=0.21). Nevertheless, exploration of the uncertainty surrounding these estimates suggests there is >90% probability that MACT is a more cost-effective strategy for reducing the recurrence of deliberate self-harm in this population over 1 year than treatment as usual. The results for quality of life were not conclusive. CONCLUSION: Cost-effectiveness acceptability curves demonstrate that, based on the evidence currently available, to reject MACT on traditional grounds of statistical significance and to continue funding current practice has <10% chance of being the correct decision in terms of cost-effectiveness.

Adult↗
PubMed2002

Identification of ARAP3, a novel PI3K effector regulating both Arf and Rho GTPases, by selective capture on phosphoinositide affinity matrices.

We show that matrices carrying the tethered homologs of natural phosphoinositides can be used to capture and display multiple phosphoinositide binding proteins in cell and tissue extracts. We present the mass spectrometric identification of over 20 proteins isolated by this method, mostly from leukocyte extracts: they include known and novel proteins with established phosphoinositide binding domains and also known proteins with surprising and unusual phosphoinositide binding properties. One of the novel PtdIns(3,4,5)P3 binding proteins, ARAP3, has an unusual domain structure, including five predicted PH domains. We show that it is a specific PtdIns(3,4,5)P3/PtdIns(3,4)P2-stimulated Arf6 GAP both in vitro and in vivo, and both its Arf GAP and Rho GAP domains cooperate in mediating PI3K-dependent rearrangements in the cell cytoskeleton and cell shape.

ADP-Ribosylation Factor 6↗
PubMed2002

Depressive symptoms predict medical care utilization in a population-based sample.

BACKGROUND: Several examinations have detected a relation between depressive symptoms and medical utilization. However, selection biases have been involved in most previous examinations. We sought to test the association between depressive symptoms and prospective, increased medical care utilization, in a population-based Canadian sample, while controlling for utilization due to medical illness and controlling for selection bias. METHODS: Data from the Nova Scotia Health Survey 1995, an age- and sex-stratified random sampling of 3227 Nova Scotian adults, included the Center for Epidemiological Studies-Depression scale and items assessing chronic medical conditions and current limitations in daily activities resulting from medical illness. We linked survey data with medical care utilization measures for the year following the survey, including out-patient visits, reimbursement for out-patient services, hospitalizations, and hospitalization days. RESULTS: After controlling for age, sex, count of medical diagnoses and current medical severity, those with a greater level of depressive symptoms were at greater risk of having increased medical care utilization in the following year. These results remained after removing mental health care utilization costs. CONCLUSIONS: In a population-based sample, depressive symptoms predicted greater medical care utilization, independent of a number of medical severity measures. Whether depressive symptoms are a risk marker or a causal risk factor for increased medical utilization remains to be explored.

Adolescent↗
PubMed2001

Early diagnosis?

Explore the source record for details and available documents.

Breast Neoplasms↗
PubMed2001

Prey selectivity and the influence of prey carbon:nitrogen ratio on microflagellate grazing.

We investigated the influence of prey species and nutritional value, in terms of carbon:nitrogen (C:N) ratio, on prey selection by the predatory microflagellate Paraphysomonas vestita. Experiments were conducted with two phytoplankton prey species of similar diameter to remove size-specific grazing effects. Live cells of both low and high C:N ratio (ranging from 4.8 to 14; N-replete and N-deplete, respectively) were offered to the predator either individually or in combination. By utilising analytical flow cytometry, we were able to enumerate the two prey species and, hence, study selective predation in the mixed-prey assemblage. In single prey experiments, the maximum observed ingestion rates were found to be higher, at all prey C:N ratios, when Isochrysis galbana was the prey item when compared to Pavlova lutheri, whilst maximum specific predator division rates were similar for both prey. Ingestion rates were influenced by prey nutrient status, higher values being observed with N-replete than N-deplete prey. When the two prey species were presented to P. vestita as a mixture, I. galbana was ingested more rapidly than P. lutheri, although ingestion was found to be suppressed when compared to when this was the sole prey species. Conversely, the presence of I. galbana did not influence the rate of ingestion of P. lutheri. P. vestita was, therefore, able to modify its rate of ingestion on the basis of prey type and prey C:N ratio and to discriminate between alternative prey of similar size in mixed-prey assemblages.

Journal Article↗
PubMed2001

Social skills performance assessment among older patients with schizophrenia.

OBJECTIVE: Social functioning is an important outcome dimension in schizophrenia. Measures of social skills frequently rely on self-report, and most measures which directly assess social functioning are time consuming. Here we describe a brief performance-based measure, the Social Skills Performance Assessment (SSPA), modified from an instrument published by Bellack et al. (Bellack, A., Morrison, R., Wixted, J., Mueser, K., 1990. An analysis of social competence in schizophrenia. Br. J. Psychiatry 156, 809--818). METHOD: 83 middle-aged and elderly patients with schizophrenia or schizoaffective disorder, and 52 normal comparison subjects (NCs) were rated on two standardized role plays, one requiring introduction to a stranger and another requiring assertive behavior with their landlord. Ratings in eight areas ranging from 'social appropriateness' to 'grooming' were made. RESULTS: SSPA required about 12 min to complete both role play and ratings, and had excellent interrater reliability, and good test-retest reliability. Patients demonstrated significantly greater disability in all areas of social functioning compared with NCs. Social performance was related to severity of negative symptoms and cognitive deficits, but not that of positive or depressive symptoms. SSPA scores were significantly correlated with health-related quality of well-being and observed performance on activities of daily living, but not to a self-reported measure of social functioning. CONCLUSION: The SSPA is a reliable and useful instrument. Direct assessment of social skills may provide a more accurate picture of functioning than self-report measures among patients who frequently lack insight into their own behavior.

Aged↗
PubMed2001

Exploring the mechanisms of action of FB642 at the cellular level.

FB642(methyl-2-benzimidazolecarbamate, carbendazim) is a systemic fungicide belonging to the benzimidazole family with antitumor activity against a broad spectrum of tumors both in vitro and in vivo such as pancreas, prostate, colon, and breast. Although the preclinical antitumor activity of FB642 has been well explored, its mechanism of action has not been as well delineated. Previous studies indicate that FB642 may interfere with mitosis and thus may disrupt or inhibit microtubule function resulting in apoptosis. This study seeks to determine if FB642 is a sufficiently novel agent worthy of further development by examining the effect of FB642 on apoptosis, the cell cycle, p53-positive and -negative tumors, and drug-resistant and MDR cell lines. The results of this present study indicate that FB642 increases the degree of apoptosis in all examined tumor cell lines, may induce G2/M uncoupling, may selectively kill p53 abnormal cells, and exhibits antitumor activity in drug- and multidrug-resistant cell lines. The induction of apoptosis by FB642, particularly in p53-deficient cells, its impressive in vivo activity against a broad spectrum of murine and human tumors, as well as an acceptable toxicity profile in animals, make FB642 an excellent candidate for further evaluation in clinical trials in cancer patients.

Animals↗
PubMed2001

Psychologic factors as precursors to hypertension.

The possibility that certain psychologic factors lead to hypertension has been considered by many investigators over the past 60 years, but prospective studies with suitable methods to evaluate this hypothesis were not available for analysis until the 1990s. There are now five large longitudinal studies demonstrating a relation between symptoms of anxiety or depression and subsequent hypertension incidence. Anger expression, long considered a major psychologic factor in hypertension, has been studied less extensively, and the findings to date are less consistent. While some evidence supports the biological plausibility of psychologic factors as risk factors for hypertension, biobehavioral mechanisms explaining the relationship have not been adequately explored. The results of these recent studies may lead to new intervention trials specifically selecting hypertensive patients with anxiety or depression for treatment with stress reduction or other appropriate psychologic therapies. Such studies would further contribute to the evaluation of anxiety and depression as risk factors for hypertension.

Anger↗
PubMed2001

Development and cross-cultural and clinical validation of a brief comprehensive scale for assessing hostility in medical settings.

This study presents the development and validation of a brief comprehensive hostility scale. Two items of each subscale from the Buss-Perry (1992) Aggression Questionnaire, most strongly correlated with their subscale score, were selected, yielding the eight-item New-Buss. Internal reliability was .66 to .81, and full and brief scales correlated r = .92 to .94. In Study 1 (95 Israeli students), New-Buss scores were significantly higher in self-rated deviant or speeding drivers than nondeviant or nonspeeding drivers, respectively. In Study 2 (279 American students), New-Buss scores correlated significantly with Barefoot's Ho, Anger-Out, Anger-In, and Agreeableness. In Study 3 (79 Israeli patients undergoing angiography), New-Buss scores were significantly correlated with coronary artery disease severity independent of SBP in men below age 60 alone but not in women. Our findings support the cross-cultural feasibility, reliability, and concurrent, construct, and criterion validity of the New-Buss.

Academic Medical Centers↗
PubMed2001

PtdIns(3)P regulates the neutrophil oxidase complex by binding to the PX domain of p40(phox).

The production of reactive oxygen species (ROS) by neutrophils has a vital role in defence against a range of infectious agents, and is driven by the assembly of a multi-protein complex containing a minimal core of five proteins: the two membrane-bound subunits of cytochrome b(558) (gp91(phox) and p22(phox)) and three soluble factors (GTP-Rac, p47(phox) and p67(phox) (refs 1, 2). This minimal complex can reconstitute ROS formation in vitro in the presence of non-physiological amphiphiles such as SDS. p40(phox) has subsequently been discovered as a binding partner for p67(phox) (ref. 3), but its role in ROS formation is unclear. Phosphoinositide-3-OH kinases (PI(3)Ks) have been implicated in the intracellular signalling pathways coordinating ROS formation but through an unknown mechanism. We show that the addition of p40(phox) to the minimal core complex allows a lipid product of PI(3)Ks, phosphatidylinositol 3-phosphate (PtdIns(3)P), to stimulate specifically the formation of ROS. This effect was mediated by binding of PtdIns(3)P to the PX domain of p40(phox). These results offer new insights into the roles for PI(3)Ks and p40(phox) in ROS formation and define a cellular ligand for the orphan PX domain.

Animals↗
PubMed2001

Group support for couples coping with a cardiac condition.

BACKGROUND/RATIONALE: Support groups of peers were designed to convey support specific to stressful situations encountered by persons with a first-time myocardial infarction and by their spouse or partners. There were no previous published support intervention studies focused on the couple. Survivors and spouses (n=28) participated in a pilot study which tested the effect of a 12-week support group intervention. DESIGN: The support groups for couples were cofacilitated by a peer and professional. The facilitators recorded field notes, while participants completed weekly diaries about the intervention activities. Following the intervention, participants were interviewed individually and facilitators were interviewed jointly about the perceived effect of the intervention and influencing factors. This article focuses on the facilitators' and participants' perceptions of intervention processes and outcomes. FINDINGS: Support processes in the group included social comparison, social learning, and social exchange. Three types of support--emotional, information, and affirmation--were provided. All participants were satisfied with the support intervention and referred to the positive effect on their coping, confidence, outlook, and spousal relationship. Factors that influenced the intervention effect were participant input, cofacilitation, similarity of group members, and the provision of information and support. CONCLUSIONS: Future interventions could consider similarity of peers, leadership, and optimum timing and duration.

Adaptation, Psychological↗
PubMed2001

Outcomes following coronary artery bypass grafting and percutaneous transluminal coronary angioplasty in the stent era: a prospective study of all 9890 consecutive patients operated on in Scotland over a two year period.

OBJECTIVE: To determine current outcomes of percutaneous transluminal coronary angioplasty (PTCA) and coronary artery bypass grafting (CABG). DESIGN: The Scottish coronary revascularisation register provided prospectively collected data on case mix and in-hospital complications for all revascularisation procedures between April 1997 and March 1999 (4775 PTCA; 5115 CABG). Linkage to routine hospital discharge and death data provided follow up information on survival and repeat revascularisation. RESULTS: Stents were used in 51% of PTCA procedures. CABG patients were older, had more severe coronary disease, and had greater comorbidity. PTCA was more likely to be undertaken as an urgent or emergency procedure. Perioperative death and urgent surgery followed 0.3% and 0.6% of PTCA procedures, respectively. Case fatality rates were higher following CABG, with 6.7% dead within two years compared with 3.4% following PTCA. PTCA was more often followed by readmission for ischaemic heart disease, repeat angiography, or revascularisation: 22.8% of patients had repeat revascularisation within two years, compared with 1.8% following CABG. CONCLUSIONS: The severity of coronary heart disease was greater than in previously published registry studies and randomised trials. Despite this, overall survival figures were comparable and repeat revascularisation rates lower, particularly following PTCA. Perioperative death and urgent surgery following PTCA were also lower. These favourable outcomes may be attributable, in part, to increased use of bail out and elective stenting.

Aged↗
PubMed2001

FENS-1 and DFCP1 are FYVE domain-containing proteins with distinct functions in the endosomal and Golgi compartments.

FENS-1 and DFCP1 are recently discovered proteins containing one or two FYVE-domains respectively. We show that the FYVE domains in these proteins can bind PtdIns3P in vitro with high specificity over other phosphoinositides. Exogenously expressed FENS-1 localises to early endosomes: this localisation requires an intact FYVE domain and is sensitive to wortmannin inhibition. The isolated FYVE domain of FENS-1 also localises to endosomes. These results are consistent with current models of FYVE-domain function in this cellular compartment. By contrast, exogenously expressed DFCP1 displays a predominantly Golgi, endoplasmic reticulum (ER) and vesicular distribution with little or no overlap with FENS-1 or other endosomal markers. Overexpression of DFCP1 was found to cause dispersal of the Golgi compartment defined by giantin and gpp130-staining. Disruption of the FYVE domains of DFCP1 causes a shift to more condensed and compact Golgi structures and overexpression of this mutant was found to confer significant protection to the Golgi against brefeldin-induced dispersal. These properties of DFCP1 are surprising, and suggest FYVE domain-localisation and function may not be exclusively endosomal. Movies available on-line

Androstadienes↗